Mini-hyper-CVD with venetoclax (Ven) for patients with relapsed/refractory (R/R) Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL): A phase II study.
Authors: Marianne Zoghbi, Elias Jabbour, Fadi Haddad, Nicholas James Short, Jayastu Senapati, Walid Macaron, Cedric Christophe Nasnas, Lewis Fady Nasr, Naveen Pemmaraju, Nitin Jain, William G. Wierda, Gautam Borthakur, Guillermo Montalban Bravo, Farhad Ravandi, Guillermo Garcia-Manero, Tapan M. Kadia, Kelly Sharon Chien, Jennifer Thankachan, Rebecca Garris, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2023)

e19039 Background: In preclinical studies, Ven has shown promising clinical activity in patients (pts) with R/R ALL. The combination of Ven with low intensity mini-HCVD chemotherapy could improve outcomes in ALL pts. Methods: Pts ≥18 years with R/R Ph-negative B- or T-cell ALL received mini-HCVD alternating with methotrexate and cytarabine for up to 8 cycles. Ven was given at a dose of 400 mg/d on Days (D) 1-14 of Cycle (C) 1 and on D1-7 of C2-8. Rituximab (if CD20+ B-ALL) and prophylactic IT chemotherapy x8 doses were given for the first 4 cycles. Pts with T-ALL received additional 2 cycles of nelarabine and peg-asparaginase during consolidation without Ven, and 2 cycles during maintenance. Maintenance with vincristine, prednisone and Ven was given for up to 2 years. Results: Between 6/2019 and 2/2021, 23 pts were treated, with a median age of 45 years (range, 20-70). 18 (78%) pts had B-ALL and 5 (22%) T-ALL, including 1 pt with ETP ALL. Among the 23 pts, the median number of prior therapies was 2 (range, 1-6) and 13 (57%) had undergone prior allogeneic stem cell transplant (ASCT). Among the 18 B-ALL pts, 16 (89%) had received prior blinatumomab and 7 (39%) prior inotuzumab. Among 23 pts, 1 was in CR at enrollment. Overall, 12 of 22 (55%) pts responded to therapy (complete response, n=9), of whom 9 achieved best response after C1 and 3 after C2. An additional pt achieved partial response. The overall response rate among the 18 pts who had at least a bone marrow assessment after C1 was 67%. The median duration of follow-up was 26 months (range, 2-35). Among the 13 responders (including the pt in CR at start), 6 (46%) relapsed, 5 (39%) underwent ASCT (4 subsequently relapsed), and 2 (15%) died in remission. The median RFS and OS were 6.4 and 8.1 months, respectively, and the 1-year RFS and OS rates were 15% and 37%, respectively. Survival was worse in pts with adverse cytogenetics versus others (median OS, 6 vs 12 months; 1-yr OS rate, 17% vs 44%; P=0.15). In C1, the median time to platelet recovery was 27 days (range, 0-81) and neutrophil recovery was 21 days (range, 0-36); in C2+, median times to recovery were 25 days (range, 0-76) and 15 days (range, 0-26), respectively. The 30-day and 60-day mortality rates were 0% and 13%, respectively. Conclusions: The combination of low-intensity chemotherapy mini-HCVD with Ven in pts with R/R Ph-negative ALL was well-tolerated and resulted in a response rate of 67%. Further studies examining the role of Ven-based therapies in ALL are needed for newly diagnosed and R/R pts. Clinical trial information: NCT03808610 . [Table: see text]